High expression of MMP14 is associated with progression and poor short-term prognosis in muscle-invasive bladder cancer.

ABSTRACT

OBJECTIVE: To evaluate the short-term prognostic value of matrix metalloproteinase 14 (MMP14) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: Expression of MMP14 and clinical information from The Cancer Genome Atlas (TCGA) were mined in MIBC patients to analyse expression differences and conduct survival analyses. The mRNA and protein expression levels of MMP14 in other tumours were analysed using Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas. The expression level of MMP14 in bladder cancer (BC) cell lines and clinical samples and its clinical significance were indicated using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), Western blotting, and immunohistochemistry. The biological functions of MMP14 were investigated by examining cell migration using in vitro wound-healing assays and cell invasion using transwell invasion assays. Survival analyses were conducted with the collected clinical follow-up data. RESULTS: Our study revealed that MMP14 is highly expressed in MIBC based, on both TCGA derived data and our clinical tissues (p<0.05). MMP14 is also highly expressed in head and neck cancer, renal cancer, pancreatic cancer and other cancers, as analysed using GEPIA and The Human Protein Atlas (p<0.05). Survival analyses of the TCGA data and our clinical follow-up data revealed high expression of MMP14 indicates a poor short-term prognosis in MIBC (p<0.05). Furthermore, downregulation of MMP14 suppressed BC cell invasion and migration abilities in vitro. MMP14 expression was closely correlated with tumour metastasis (p<0.05). T stage [hazard ratio (HR)=1.412, 95% confidence interval (CI)=1.121-1.779, p=0.003] and metastasis (HR=2.256, 95% CI=1.242-4.100, p=0.008) were unfavourable prognostic factors in BC patients. CONCLUSIONS: In MIBC, MMP14 expression is upregulated and closely associated with disease progression and poor short-term prognosis.